Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

No-Directional and Backward-Leak Uni-Directional Updatable Encryption Are Equivalent

Updatable encryption (UE) enables the cloud server to update the previously sourced encrypted data to a new key with only an update token received from the client. Two interesting works have been proposed to clarify the relationships among various UE security notions. Jiang (ASIACRYPT 2020) proved the equivalence of every security notion in the bi-directional and uni-directional key update settings and further, the security notion in the no-directional key update setting is strictly stronger than the above two. In contrast, Nishimaki (PKC 2022) proposed a new definition of uni-directional key update that is called the backward-leak uni-directional key update, and showed the equivalence relation by Jiang does not hold in this setting. We present a detailed comparison of every security notion in the four key update settings and prove that the security in the backward-leak uni-directional key update setting is actually equivalent to that in the no-directional key update setting. Our result reduces the hard problem of constructing no-directional key update UE schemes to the construction of those with backward-leak uni-directional key updates.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Cyber Securit

Your Smart Contracts Are Not Secure: Investigating Arbitrageurs and Oracle Manipulators in Ethereum

Smart contracts on Ethereum enable billions of dollars to be transacted in a decentralized, transparent and trustless environment. However, adversaries lie await in the Dark Forest, waiting to exploit any and all smart contract vulnerabilities in order to extract profits from unsuspecting victims in this new financial system. As the blockchain space moves at a breakneck pace, exploits on smart contract vulnerabilities rapidly evolve, and existing research quickly becomes obsolete. It is imperative that smart contract developers stay up to date on the current most damaging vulnerabilities and countermeasures to ensure the security of users' funds, and to collectively ensure the future of Ethereum as a financial settlement layer. This research work focuses on two smart contract vulnerabilities: transaction-ordering dependency and oracle manipulation. Combined, these two vulnerabilities have been exploited to extract hundreds of millions of dollars from smart contracts in the past year (2020-2021). For each of them, this paper presents: (1) a literary survey from recent (as of 2021) formal and informal sources; (2) a reproducible experiment as code demonstrating the vulnerability and, where applicable, countermeasures to mitigate the vulnerability; and (3) analysis and discussion on proposed countermeasures. To conclude, strengths, weaknesses and trade-offs of these countermeasures are summarised, inspiring directions for future research. Cyber Securit

VAL: Volume and Access Pattern Leakage-Abuse Attack with Leaked Documents

Searchable Encryption schemes provide secure search over encrypted databases while allowing admitted information leakages. Generally, the leakages can be categorized into access and volume pattern. In most existing SE schemes, these leakages are caused by practical designs but are considered an acceptable price to achieve high search efficiency. Recent attacks have shown that such leakages could be easily exploited to retrieve the underlying keywords for search queries. Under the umbrella of attacking SE, we design a new Volume and Access Pattern Leakage-Abuse Attack (VAL-Attack) that improves the matching technique of LEAP (CCS ’21) and exploits both the access and volume patterns. Our proposed attack only leverages leaked documents and the keywords present in those documents as auxiliary knowledge and can effectively retrieve document and keyword matches from leaked data. Furthermore, the recovery performs without false positives. We further compare VAL-Attack with two recent well-defined attacks on several real-world datasets to highlight the effectiveness of our attack and present the performance under popular countermeasures.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Cyber Securit

Mechanisms of autogenous shrinkage of alkali-activated slag and fly ash pastes

This study aims to provide a better understanding of the autogenous shrinkage of slag and fly ash-based alkali-activated materials (AAMs) cured at ambient temperature. The main reaction products in AAMs pastes are C-A-S-H type gel and the reaction rate decreases when slag is partially replaced by fly ash. Due to the chemical shrinkage and the fine pore structure of AAMs pastes, drastic drop of internal relative humidity is observed and large pore pressure is generated. The pore pressure induces not only elastic deformation but also a large creep of the paste. Besides the pore pressure, other driving forces, like the reduction of steric-hydration force due to the consumption of ions, also cause a certain amount of shrinkage, especially in the acceleration period. Based on the mechanisms revealed, a computational model is proposed to estimate the autogenous shrinkage of AAMs. The calculated autogenous shrinkage matches well with the measured results.Materials and Environmen

Effect of CaO content in raw material on the mineral composition of ferric-rich sulfoaluminate clinker

Ferric-rich calcium sulfoaluminate (FR-CSA) cement is an eco-friendly cement. Fe2O3 exists in different minerals of FR-CSA clinker, e.g., Ca4Al2Fe2O10 (C4AF), Ca2Fe2O5 (C2F), and Ca4Al6-2xFe2xSO16 (C4A3-xFxS-). The mineral composition depends on the chemical composition of the raw materials and significantly determines the reactivity of FR-CSA cement. To optimize the phase composition of the FR-CSA clinker, chemical reagent raw mixtures with different amounts of CaO were used to prepare the FR-CSA clinker. X-ray diffraction (XRD) analysis, Rietveld quantitative phase analysis (RQPA), Fourier Transform Infrared spectroscopy (FT-IR), and scanning electron microscopy/energy-dispersive spectroscopy (SEM/EDS) were used to identify the mineralogical conditions of the FR-CSA clinker. The results indicated that the amounts of CaO in raw materials greatly affected the iron-bearing phase formation in the FR-CSA clinker. With decreasing CaO content involved in calcination reaction, the amounts of Fe2O3 incorporated in C4A3-xFxS- increased up to 17.72 wt% (where x = 0.36). The findings make it possible to optimize the mineral composition of the FR-CSA clinker by changing the CaO content in raw materials. Furthermore, low CaO content in the raw material is beneficial to the formation of C4A3-xFxS-, which enables the use of solid wastes containing low calcium for producing FR-CSA cement.Accepted author manuscriptMaterials and Environmen

Random voids generation and effect of thermal shock load on mechanical reliability of light-emitting diode flip chip solder joints

To make the light-emitting diode (LED) more compact and effective, the flip chip solder joint is recommended in LED chip-scale packaging (CSP) with critical functions in mechanical support, heat dissipation, and electrical conductivity. However, the generation of voids always challenges the mechanical strength, thermal stability, and reliability of solder joints. This paper models the 3D random voids generation in the LED flip chip Sn96.5-Ag3.0-Cu0.5 (SAC305) solder joint, and investigates the effect of thermal shock load on its mechanical reliability with both simulations and experiments referring to the JEDEC thermal shock test standard (JESD22-A106B). The results reveal the following: (1) the void rate of the solder joint increases after thermal shock ageing, and its shear strength exponentially degrades. (2) the first principal stress of the solder joint is not obviously increased, however, if the through-hole voids emerged in the corner of solder joints, it will dramatically increase. (3) modelling of the fatigue failure of solder joint with randomly distributed voids utilizes the approximate model to estimate the lifetime, and the experimental results confirm that the absolute prediction error can be controlled around 2.84%.Electronic Components, Technology and Material

Utilization of biomass fly ash in alkali-activated materials

This paper investigated the feasibility of using biomass fly ash (BFA) to prepare alkaliactivated slag and fly ash paste. The reference mixture was alkali-activated slag and coal fly ash (CFA) paste with a slag-to-coal fly ash ratio of 50/50. In other mixtures, coal fly ash was replaced at 40% and 100% with BFA, respectively. The results showed that the incorporation of BFA accelerated the setting of the paste, while its impact on the compressive strength was minor. XRD and FTIR results indicated that the BFA participated in the reaction process. BFA showed potential use as CFA replacement in synthesizing alkali-activated materials, which would pave a way for the valorisation of BFA.Materials and Environmen

Luminescence of Ce3+ activated fluoro-apatites M5(PO4)3F (M = Ca, Sr, Ba) under VUV—UV and x-ray excitation

Applied Science

Autogenous deformation induced- stress evolution in high-volume GGBFS concrete: Macro-scale behavior and micro-scale origin

This study aims to experimentally investigate the autogenous deformation and the stress evolution in restrained high-volume ground granulated blast furnace slag (GGBFS) concrete. The Temperature Stress Testing Machine (TSTM) and Autogenous Deformation Testing Machine (ADTM) were used to study the macro-scale autogenous deformation and stress evolution of high-volume GGBFS concrete with w/b ratios of 0.35, 0.42, and 0.50. The early-age cracking (EAC) risk (quantified by stress-strength ratio) and stress relaxation were analyzed extensively based on ADTM and TSTM results. Furthermore, Environmental Scanning Electron Microscopy (ESEM), X-ray Diffraction (XRD), and Mercury Intrusion Porosimetry (MIP) were conducted to explore the micro-scale origin of the autogenous deformation of high-volume GGBFS concrete, which supports the observations on the macroscale measurement of TSTM/ ADTM tests. This study finds that the ettringite formation in the first two days results in autogenous expansion, which can delay the appearance of tensile stress. The magnitude of autogenous expansion depends on the compatibility of ettringite content and pore size. The w/b ratio of 0.42 turns out to be optimal because it produces the highest amount of ettringite and results in the highest autogenous expansion. In comparison, the w/b ratio of 0.35 introduces significant autogenous shrinkage after the expansion peak and therefore corresponds to a high early-age cracking risk.Materials and EnvironmentConcrete Structure